Wound healing is an intricate, orchestrated process involving the interactions of various cells and matrix components to first establish a provisional tissue and then remodel this while forming the mature replacement. Initially, the hemostatic platelet plug reestablishes the infection-limiting and desiccation-limiting barrier, and elicits the first wave of cellular infiltrates. This consists mainly of leukocytes that provide both innate and acquired immunity. These cells produce enzymes and biocidal molecules to eliminate microbial contamination; however, these same defense mechanisms are detrimental to the keratinocytes, fibroblasts and endothelial cells required to regenerate the lost tissue. Thus, as healing proceeds, the events and processes of the inflammatory phase need to regress.
A particular challenge is offered in the case of skin wound repair, which occurs at a contaminated surface. If a wound becomes infected, the normal healing is disrupted as the inflammatory phase becomes chronic, suppressing the regenerative phase. Further, the enzymes liberated by both the microbes and leukocytes break down the wound tissue as well as surrounding skin. Thus, it is critical to ensure proper healing to prevent infections being established by normal skin wound contaminants.
Wound healing is usually divided into three phases: the inflammatory phase, the proliferative phase, and the remodeling phase. Fibronectin has been reported to be involved in each stage of the wound healing process, particularly by creating a scaffold to which the invading cells will adhere. Initially, there is a release of many mediators to the wound site, such as fibronectin and fibrinogen. Fibronectin promotes inflammatory cell migration into the wound and debris phagocytosis by monocytes. Thereafter, angiogenesis and reepithelialization take place. At this stage, fibronectin exerts chemotactic activity on endothelial cells, and promotes epithelial cell and fibroblast migration onto the basal membrane. Fibronectin also appears to be essential in the remodeling phase where it plays a major role in the organization of collagen fibrils. The fibrillar collagen ultimately forms fibrous bundles that enhance the tissue tensile strength, leading to would closure.
Hydro gels have typically been utilized as topical formulations for promoting the wound healing process. The gel compositions have been selected for their properties of swelling degree, biocompatibility, permeability, and swelling kinetics. Examples of such compounds have included vinyl polymers (e.g. polyacrylic acid), cellulose, and cellulose derivatives. Polyacrylic acid polymer, also referred to as carbomer, has been used because of its superiority in delivering fibronectin to skin wounds.
Naturally occurring biopolymers have applications in tissue engineering, regenerative medicine, drug delivery, medical implant, plastic surgery, and others. Such products have components including hyaluronic acid (HA), chitosan, heparin, chondroitin sulfate, alginate and other glucosamine and glycosaminoglycans, other polysaccharides, and derivatives thereof.
In combination, concentrations of fibronectin (and similar proteins) have been utilized with alginate salt to treat chronic ulcers. The dressing system has been solidified, converting the gel into fibers, by a process of freeze-drying. This procedure creates a sponge-like structure with hydrophilic properties. In the presence of fluids, the dressings can return to a gel-like state, absorbing up to 20 times their weight in wound exudate. The dressing is easily removed after the wound treatment because of its sponge-like structure and moisture retention. However, once hydrated with saline solution, the fibronectin-cellulose dressing does not provide the desired fibrous protective film on the surface of the deepithelialized human skin. Debridement is then performed upon removal of the dressing to remove any necrotic material.
Thus, problems exist in the treatment of acute and chronic wounds, including delayed healing, reduced granulation and epithelialization, and persistent wound inflammation. Compromised wound healing can result in other complications and problems, such as infection, pain, and development of chronic (non-healing) wounds.
Current needs exist in the treatment of chronic wounds which would assist healing, decrease inflammation, reduce pain, and prevent scar formation with both acute and chronic wounds. Such acute wounds that could be treated include burns, abrasions, dry skin, post-op surgical incisions, cuts, puncture wounds, blisters, insect bites, and other severe tissue injury. Chronic wound treatment might encompass slow to heal wounds including pressure ulcers, venous ulcers, diabetic foot ulcers, decubitus ulcers, and non-healing tissue injuries.
Overall, a composition is desired that will be easily applied, forming a matrix conducive to the healing of a tissue, and having anti-microbial properties. The composition may be biocompatible or quickly reacted to avoid possibilities of cytotoxicity. Further, the composition will stimulate and maximize wound healing while providing a controlled method for providing thin and thick layers of a solidified wound dressing, as desired.
Indirect effects may include reduced need for medical procedures such as debridement, decreased hospitalization time, reduced postoperative recovery times, shortened return interval to daily functions and work, and reduced overall treatment costs. Desirably, these improvements to wound healing, including application and method of use, will be valuable in treating and repairing various tissue(s).